糖尿病小鼠肝线粒体氧化损伤及其机制

Hepatica Mitochondrial Oxidative Injures and Machinates in Diabetic Mouse

目的:糖尿病是威胁人类健康的主要疾病之一,为了证明糖尿病的发生发展与氧化应激密切相关,从线粒体呼吸链角度探讨其机制。方法:用四氧嘧啶(Alloxan)建立实验性糖尿病小鼠模型,利用比色法分别从整体、组织和线粒体水平测定抗氧化酶活性,用铁氰化钾脉冲法测定线粒体呼吸活链II+III电子传递与质子泵出偶联(H+/2e)。结果:糖尿病小鼠GSH、GSH-Px分别比对照组显著降低(P<0.001),血清和肝组织、线粒体GSH-Px/MDA比值分别降低59.89%、40.69%和59.65%;线粒体呼吸链II+III总H+/2e显著降低24.76%(P<0.05),净H+/2e显著降低32.31%(P<0.05)。结论:实验性糖尿病小鼠肝功能损伤是氧化性损伤,氧化应激又是该损伤的结果,其原因与质子漏增加,电子传递与质子泵出脱偶联有关,导致自由基增加,无效耗氧增加,线粒体受损。

Objective：Diabetes is one of the main diseases threatening human being＇s health. To research the occurrence and development of diabetes is much concerned with oxidative irritability and contain the mechanism from the mitochondrial angle. Methods： We constructed Model of diabetes with Alloxan in mouse, and determine the activity of antioxidant enzyme and the activity of respiration respectively in blood, liver tissue, and mitochondria. We also designed to determine the parameter of liver mitochondria about Rate of electron transfer to proton pump of mitochondrial respiratory chain complex Ⅱ ＋Ⅲ （H^＋/2e）. Result. In Diabetic mouse , the GSH content, GSH-Px activity decreased obviously （P〈0. 001） ; the rate of GSH-Px/ MDA decreased by 59. 89%, 40. 69% , 59. 65% respectively in blood, liver tissue and liver mitochondria; the total and net H^＋/2e of complex Ⅱ ＋ Ⅲdecreased by 24. 76 and 32. 31 %（respectively , P〈0. 05）. Conclusion： the damage from diabetes is oxidative damage, and oxidative irritability is the result of this damage. Mitochondrial proton leak, the decreased coupling of electron transfer andproton pump , and the increase of oxygen free radical, the ineffective increase of oxygen consumption might be responsible for the decreased mitochondrial efficiency of oxygen utilization.